Poster presentation

Chronic arthritis is characterized by persistent joint inflammation and concomitant
joint destruction. IL-17 is a novel proinflammatory T-cell cytokine suspected to be
involved in inflammatory and autoimmune diseases such as rheumatoid arthritis. Here,
we report that IL-17 receptor (IL-17R) signaling is required in resident synovial
cells for full progression of chronic synovitis and bone erosion. Repeated injections
of Gram-positive bacterial cell wall fragments (SCW) directly into the knee joint
of naïve IL-17R-deficient (IL-17R-/-) mice had no effect on the acute phase of arthritis but prevented progression to
chronic destructive synovitis as was noted in wild-type (wt) mice. Micro-array analysis
revealed significant down-regulation of leukocyte-specific chemokines, selectins,
collagenase-3, and IL-1 in the synovium of IL-17R-/- mice. Bone marrow (BM) chimeric mice revealed the need for IL-17/IL-17R signaling
in resident synovial cells for development of full blown synovitis. Chimeric mice
of host wt and donor IL-17R-/- BM cells developed destructive synovitis in this chronic relapsing SCW arthritis model
similar to wt → wt chimeras. In contrast, chimeric mice of host IL-17R-/- and donor wt BM cells were protected from full blown destructive arthritis similar
to IL-17R-/- → IL-17R-/- chimeras. These data strongly suggest T-cell IL-17-IL-17R signaling in resident synovial
cells to be a pivotal mechanism through which an acute macrophage-driven joint inflammation
progresses into a chronic destructive synovitis. Prevention of local synovial IL-17-IL-17R
signaling warrants consideration as a therapeutic target in chronic destructive arthritis.